Nanozyme sensor array based on manganese dioxide for the distinction between multiple amyloid β peptides and their dynamic aggregation process

Abstract

The determination of the amyloid β (Aβ) peptide and its aggregation intermediates helps to understand the pathological mechanism of Alzheimer's disease (AD) caused by toxic amyloid fragments. Because of the transient and heterogeneous properties of Aβ aggregates, it is very difficult to dynamically detect Aβ and its aggregation intermediates. Herein, we successfully constructed a two-dimensional manganese dioxide (MnO₂) nanozyme sensor array by modulating the peroxidase-mimicking activity using various Aβ species and accurately distinguished among six types of Aβ within 1 h through linear discriminant analysis (LDA), with a dynamic detection range of 0.01-500 nmol/L and a detection limit of 0.44 pmol/L. Subsequently, 30 unknown blind samples were used to verify the practicability of the sensor array, and all unknown samples were identified with 100% accuracy. It is worth noting that the sensor array successfully distinguished healthy individuals from AD patients using clinical blood samples. This study provides a convenient and reliable nanozyme biosensing system for detecting Aβ species and their related aggregation processes.

Keywords: Alzheimer's disease; Amyloid β; Dynamic aggregation; Manganese dioxide nanozyme; Sensor array.